Organ Transplantation

Caroline Tassey MS, CPNP

INTRODUCTION

Organ transplant has expanded the treatment options available to children with end-stage disease, structural anomalies incompatible with life, and refractory malignancies. About 2000 infants, children, and adolescents are currently waiting for solid organ transplant (all statistics are from United Network for Organ Sharing [UNOS] and are available on their website at www.unos.org). Of these, approximately one third are infants and children younger than 6 years. Bone marrow transplant (BMT) is no longer a treatment of last resource but an increasingly standard treatment for recurrent childhood leukemias. Survival rates for all transplants have increased significantly over the past 10 to 15 years. New techniques, such as partial organ transplant, have expanded recipient options. As a result, the primary care provider can expect to care for one or more children who are awaiting or have undergone transplant. While all these children will be followed by subspecialists and, in varying degrees, by the transplant center, they continue to require good, consistent primary care. This chapter describes the transplant process and transplant-related complications. This information will help the provider in the support and collaborative management of the patient and family.

PATHOLOGY AND EPIDEMIOLOGY

Kidney

End stage renal disease of diverse etiology is the primary indication for renal transplant. Reasons for transplant need include structural anomalies and inborn errors of metabolism. More than 600 pediatric renal transplants were performed in 1997 (Feber et al., 1998; D’Alessandro et al., 1998). Among adolescents on the transplant waiting list, the largest group—43%—are waiting for a kidney (Salvatierra et al., 1997; Feber et al., 1998; Salvatierra et al., 1998). The kidney plays an important role in physical growth. Therefore, kidney transplant in a younger child, before growth has been stunted, improves the chance for attaining normal height (Feber et al., 1998). Refer to Chapter 62 for further detail about the kidneys’ role in growth.

Donor kidneys are placed in the abdomen rather than in the retroperitoneal space. Therefore, the size of the graft is not important. Adult kidneys can be used for all but the smallest infants. At 7 to 10 kg, most infants can accept an adult kidney. In fact, survival of infants who receive adult-sized kidneys is higher than those transplanted with size-compatible pediatric kidneys (Salvatierra et al., 1998). Patient survival with an organ from a living related donor (LRD), usually a parent, is 96% at 1 year; 5-year survival is 93%. Graft survival rates are lower (84% and 65%), but graft failure can be managed with dialysis and retransplant. Cadaver donor transplants are generally less successful. The oldest survivor of a pediatric kidney transplant received an LRD kidney at 14 years of age in 1963. As of 1998, this recipient has had 35 years of continuous graft function. Overall, pediatric renal transplant has been so successful that virtually any child with chronic renal failure should be considered a candidate regardless of age, size, or etiology of renal failure (Salvatierra et al., 1997; UNOS, 1997–1998).

Liver

Indications for liver transplant include congenital malformations, metabolic liver disease, neoplasms without metastases, and liver failure of diverse etiology. Early transplant of the liver-pancreas is also indicated for children with cystic fibrosis whose lung disease is only moderate (Kelly, 1998). About 550 pediatric liver transplants were performed in 1997 (Boucek et al., 1997). The largest number of infants and children up to 10 years of age on the transplant waiting list are waiting for a liver (54% and 45%, respectively) (UNOS, 1999).

The ability to use reduced-size liver transplants by splitting a harvested organ or transplanting only one lobe has reduced waiting time for recipients, improved options for neonates and infants, and allowed the use of LRDs. Neonates under 10 kg can undergo partial liver transplant; the youngest surviving recipient was 12 days old. The current trend is to transplant earlier, before development of significant growth or psychosocial retardation (Zitelli, 1986). Malnutrition is a common complication of chronic liver failure and adversely affects survival after transplant. One-year survival is currently 80%; 5-year survival is 76%. However, longer-term survival should improve with the use of LRD organs (UNOS, 1997–1998).

Heart

Indications for pediatric heart transplant include congenital structural cardiac anomalies and cardiomyopathy, both congenital and acquired. Almost 300 heart transplants were performed in 1997 (Boucek et al., 1997). Infants younger than 1 year account for almost 33% of all heart transplant recipients. Structural congenital heart disease (CHD) is the transplant indication for 75% of these infants. In children up to 10 years of age, CHD and myopathy account for 40% and 60% of transplants, respectively. By adolescence, the most common reason for heart transplant (65%) is cardiomyopathy (Boucek et al., 1997).

Unfortunately, the volume of heart transplants has not changed much since 1990. About one third of listed infants die awaiting a heart (Morrow et al., 1997). The major limiting factor to successful heart transplantation in infants and young children is the limited supply of donors. Further, size concurrence is critical in pediatric heart transplant. The donor heart and great vessels are grafted to the recipient’s right atrial appendage and great vessels. If the donor organ
is too large, the sternum cannot be closed. The donor heart contains its own functioning sinoatrial node. There is no connection between the recipient’s autonomic nervous system and the donor heart.

Early mortality after heart transplant remains high, ranging from 12% to 24%. Survival is best in the adolescent group (80% at 1 year) and worst in the infant group (70% at 1 year), although some centers specializing in infant transplant report better results. The Loma Linda group reports infant survival as 91% at 1 month, 84% at 1 year, 78% at 5 years, and 70% at 7 years (Morrow et al., 1997). By 5 years post-transplant, no age difference is seen in survival rates. Five-year survival is 60% (Boucek et al., 1997; Canter et al., 1997).

Lung

Indications for pediatric lung transplant include congenital pulmonary fibrosis, primary pulmonary hypertension, inborn errors of metabolism, cystic fibrosis, and chronic obstructive pulmonary disease, often secondary to CHD. In the adolescent group, cystic fibrosis is the most common indication for transplant (63%). No single indicator predominates in younger age groups (UNOS, 1997–1998).

Both single-lung and bilateral lung transplants are performed. Size match is not critical. If there is a difference in donor and recipient lung capacity, the transplanted lung will adjust to new surroundings. Sequential single-lung transplant is commonly used for recipients with cystic fibrosis. Children with CHD and pulmonary vascular disease require heart-lung transplantation.

Mortality after lung transplant remains high. One-year survival for all age groups is 70%; 4-year survival is 50% (Boucek et al., 1997). One-year survival for heart-lung recipients is 59%. The longest survival time after pediatric lung transplant is currently 6½ years (UNOS, 1997–1998).

Bone Marrow

Bone marrow transplant is now an accepted therapeutic option for children with a variety of diseases. These include leukemias and other malignancies, as well as several hematologic and immunodeficiency diseases. BMT is the treatment of choice for children who relapse from conventional chemotherapy for mylogenous leukemias in first remission or in chronic phase (Sanders, 1997). Donor marrow is obtained by multiple needle aspirations and infused intravenously into the recipient. The donor’s risk is low, although complications from anesthesia and infection have occurred. Donors may be hospitalized overnight. The recipient is pretreated with high-dose chemotherapy and total body irradiation to produce immunosuppression. There are no lower age limits for either recipients or donors, but there are a limited number of pediatric BMT centers.

Mortality remains high. Even in a perfect human leukocyte antigen (HLA)-matched donor-recipient relationship, both acute and chronic graft-versus-host disease (GVHD) can occur. Not all histocompatibility antigens have yet been identified. Five-year event-free survival currently ranges from 38% to 59%, and is dependent on the initial indication for transplant. Children with acute lymphocytic leukemia in second remission who receive allogenic sibling BMT have the lowest mortality (Gordon et al., 1997; Sanders, 1997).

A successful transplant depends on matching the recipient’s genetic HLA haplotype with that of a donor. HLA antigens are responsible for the self-specific immune response. HLA antigens vary greatly among individuals. There are three types of BMT. Autologous transplants use marrow previously harvested from the recipient. Syngeneic transplants use marrow harvested from an identical twin. Allogenic transplants are the most common type, using marrow from a donor who has the same histocompatibility antigens as the recipient. Usually, but not always, a sibling, parent, or other relative is the marrow donor.

Table 66-1 provides a summary of transplant survival rates at 1 year postsurgery.

HELPING THE CHILD AND FAMILY PREPARE FOR TRANSPLANT

Logistical and Practical Issues

Generally, children are considered for transplant when their quality of life begins to deteriorate and their potential life-span is no more than 1 to 2 years. Most children are already followed by a subspecialist who will make the decision to refer for transplant. Neonates who require heart transplant for complex, single-ventricle defects are listed at birth if the family does not choose or the infant is not a candidate for palliation. Not every child referred for transplant will be listed. Patients and their families undergo extensive medical and psychosocial evaluation by a team consisting of medical specialists, psychologists, clinical nurse specialists, pharmacists, social workers, and others. The family’s ability to follow
the post-transplant treatment regimen and to manage the economic and psychosocial impact of the process is an important consideration.

Immunologic testing may suggest that an individual child is unlikely to match with more than 1% to 2% of donors (Stiehm, 1996; Yunis & Dupont, 1993). Children have a poorer chance of being listed if they have active infections, such as human immunodeficiency virus; significant systemic disease, such as diabetes; or chromosomal or genetic abnormalities with poor long-term prognosis.

Once listed, children are designated status I or status II. Status I individuals have priority in the allocation of available organs. To qualify as status I, a child must be hospitalized in the intensive care unit, requiring mechanical ventilation, or intravenous inotropic therapy. Infants younger than 6 months are automatically designated status I. There is no status I for lung (and heart-lung) recipients.

The waiting time for an organ to become available is difficult to predict. Currently, time spent on the list varies significantly from one transplant center to another. For example, patients listed (all organs) at the University of Pittsburgh Medical Center wait 721 days on average, while those listed at the Medical University of South Carolina average a 136-day wait (Langley, 1999). However, new U.S. Department of Health and Human Services regulations may change how donated organs are allocated in the near future. These regulations would establish a national registry and require donated organs to be distributed across the country to the sickest patients. The impact this change will have on pediatric patients waiting for organs remains to be seen.

Transportation time to the transplant center for both the organ and the child can affect waiting time. The window of opportunity between notification that an organ is available and the child’s arrival in the operating suite varies by organ. Some families choose or are required to move closer to the transplant center to be ready when an organ becomes available. In reality, this usually means that one parent and the child maintain a residence near the transplant center, while the other parent and any siblings live at home.

Emotional and Ethical Issues

Waiting for an organ is emotionally difficult for families. Parents feel exhilarated when their child is listed, anxious and impatient as they wait, and then depressed while watching their child become sicker and wondering if an organ will become available. They experience relief and excitement when one does, and they also feel guilty, knowing that they are waiting for another parent’s child to die. During the long period of waiting for an organ, the primary care provider is a major source of support, counseling, and knowledge of community resources.

The family experiences unique stresses when a family member is considered for donation or becomes the organ donor. Serious complications to the solid (ie, replaced) organ donor are rare, but the risks of surgery, anesthesia, and acute or chronic organ dysfunction do exist. For example, liver function of the partial liver donor is affected in the immediate postoperative period (Tojimbara et al., 1998). The use of minor siblings as organ donors remains an ethical issue, although most primary care providers now accept the parents’ right to consent to bone marrow extraction from siblings, including infants older than 6 months, even when the likelihood of successful transplantation is poor (Chan et al., 1996). When a graft is rejected or fails, the sibling or parent donor may experience guilt and distress (Shama, 1998). Sibling donors report higher levels of anxiety and lower levels of self-esteem than nondonor siblings (Packman et al., 1997).

MANAGEMENT

Helping the Child and Family Post-transplantation

Duration of hospitalization after solid organ transplant is 2 to 4 weeks. BMT recipients will be hospitalized for 4 to 6 weeks and will be quite ill during the first 2 to 3 weeks because of the pretransplant conditioning. The transplanted marrow will take 2 to 3 weeks to begin providing effective immunity. Programs have varying requirements for extended stay near the transplant center after discharge. Extended stay is necessary to provide frequent monitoring and close supervision of the immunosuppressant regimen. This period may last for several months. The financial burden for maintaining this second home falls largely on the recipient’s family. Family finances and family separation are the biggest parental stressors during the transplant process (Rodrigue et al., 1996). The average cost of pediatric BMT, for example, is $100,000 to $250,000 (Yoder, 1998). Solid organ transplant costs exceed $100,000. Third-party payers will not provide all of the cost of transplant.

It is the primary care provider’s responsibility to optimize child and family health during this waiting period. The provider is key in preparing the family for living with an immunosuppressed member. It is very common for families to view transplant as a panacea. They need to understand that transplant is not a cure. For example, although BMT may offer a full return to health, solid organ transplantation trades one chronic illness for another—albeit a more manageable one with a better long-term prognosis.

Vaccinations

Immunosuppression will affect the child’s ability to be vaccinated and increase his or her risk when exposed to common contagious diseases. Every effort should be made to complete appropriate vaccination series prior to transplant (vaccination recommendations following the American Academy of Pediatrics 2000 Red Book: Report of the Committee on Infectious Diseases; individual transplant centers may have specific recommendations). In particular, hepatitis B vaccination and all live-virus vaccinations (measles-mumps-rubella [MMR], varicella) should be completed if possible. When feasible, immunizations should be given no later than 1 month before transplant to allow an adequate antibody response before immunosuppression. Hepatitis A immunization is not routinely recommended for recipients.

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